Ozone dynamics in a Mediterranean Holm oak forest: comparison among transition periods characterized by different amounts of precipitation

Tropospheric ozone (O3) is one of the most toxic compounds for plants in the atmosphere. The large amount of anthropogenic O3 precursors in the urban areas promote O3 formation, thus making Mediterranean forests located in periurban areas particularly vulnerable to this pollutant. O3 flux measurements have been carried out using the Eddy Covariance technique over a Holm oak forest located 25 Km from Rome downtown, inside the Presidential Estate of Castelporziano (Italy).Two transition periods - early Spring and late Fall - in two consecutive years were examined. The uncommon low precipitation recorded in both transition periods in 2012 allowed to evaluate the influence of water availability on O3 fluxes during seasons which are not commonly affected by drought stress.Overall, the forest canopy showed to be a net sink of O3, with peak values of mean daily O3 fluxes of -8.9 nmol m-2s-1 at the beginning of flowering season and -4.6 nmol  m-2s-1 at the end of Fall.O3 fluxes were partitioned between stomatal and non stomatal sinks using the evaporative/resistive method based on canopy transpiration in analogy with an Ohm circuit. By comparison of the two years, water availability showed to be an important limiting factor during Spring, since in this season plants are more photosynthetically active and more sensitive to water availability, while in Fall, under conditions of low stomatal conductance,  the dependence on water availability was less appreciated

Ecophysiological Responses to Rainfall Variability in Grassland and Forests Along a Latitudinal Gradient in Italy

In the Mediterranean region, ecosystems are severely affected by climate variability. The Italian Peninsula is a hot spot for biodiversity thanks to its heterogeneous landscape and the Mediterranean, Continental, and Alpine climates hosting a broad range of plant functional types along a limited latitudinal range from 40\u2032 to 46\u2032 N. In this study we applied a comparative approach integrating descriptive statistics, time series analysis, and multivariate techniques to answer the following questions: (i) do the climatic variables affect Gross Primary Productivity (GPP), Reco, Water Use Efficiency (WUE), and ET to a similar extent among different sites? (ii) Does a common response pattern exist among ecosystems along a latitudinal gradient in Italy? And, finally (iii) do these ecosystems respond synchronically to meteorological conditions or does a delayed response exist? Six sites along a latitudinal, altitudinal, and vegetational gradient from semi-arid (southern Italy), to a mountainous Mediterranean site (central Italy), and sub-humid wet Alpine sites (northern Italy) were considered. For each site, carbon and water fluxes, and meteorological data collected during two hydrologically-contrasting years (i.e., a dry and a wet year) were analyzed. Principal Component Analysis (PCA) was adopted to identify temporal and spatial variations in GPP, Ecosystem Respiration (Reco), WUE, and Evapotranspiration (ET). The model outlined differences among Mediterranean semi-arid, Mediterranean mountainous, and Alpine sites in response to contrasting precipitation regimes. GPP, Reco, WUE, and ET increased up to 16, 19, 25, and 28%, respectively in semi-arid Mediterranean sites and up to 15, 32, 15, and 11%, respectively in Alpine sites in the wet year compared to the dry year. Air temperature was revealed to be one of the most important variables affecting GPP, Reco, WUE, and ET in all the study sites. While relative air humidity was more important in southern Mediterranean sites, global radiation was more significant in northern Italy. Our work suggests that a realistic prediction of the main responses of Italian forests under climate change should also take in account delayed responses due to acclimation to abiotic stress or changing environmental conditions

Measurable Residual Disease (MRD) as a Surrogate Efficacy-Response Biomarker in AML

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal postremission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint

Ecophysiological Responses to Rainfall Variability in Grassland and Forests Along a Latitudinal Gradient in Italy

In the Mediterranean region, ecosystems are severely affected by climate variability. The Italian Peninsula is a hot spot for biodiversity thanks to its heterogeneous landscape and the Mediterranean, Continental, and Alpine climates hosting a broad range of plant functional types along a limited latitudinal range from 40′ to 46′ N. In this study we applied a comparative approach integrating descriptive statistics, time series analysis, and multivariate techniques to answer the following questions: (i) do the climatic variables affect Gross Primary Productivity (GPP), Reco, Water Use Efficiency (WUE), and ET to a similar extent among different sites? (ii) Does a common response pattern exist among ecosystems along a latitudinal gradient in Italy? And, finally (iii) do these ecosystems respond synchronically to meteorological conditions or does a delayed response exist? Six sites along a latitudinal, altitudinal, and vegetational gradient from semi-arid (southern Italy), to a mountainous Mediterranean site (central Italy), and sub-humid wet Alpine sites (northern Italy) were considered. For each site, carbon and water fluxes, and meteorological data collected during two hydrologically-contrasting years (i.e., a dry and a wet year) were analyzed. Principal Component Analysis (PCA) was adopted to identify temporal and spatial variations in GPP, Ecosystem Respiration (Reco), WUE, and Evapotranspiration (ET). The model outlined differences among Mediterranean semi-arid, Mediterranean mountainous, and Alpine sites in response to contrasting precipitation regimes. GPP, Reco, WUE, and ET increased up to 16, 19, 25, and 28%, respectively in semi-arid Mediterranean sites and up to 15, 32, 15, and 11%, respectively in Alpine sites in the wet year compared to the dry year. Air temperature was revealed to be one of the most important variables affecting GPP, Reco, WUE, and ET in all the study sites. While relative air humidity was more important in southern Mediterranean sites, global radiation was more significant in northern Italy. Our work suggests that a realistic prediction of the main responses of Italian forests under climate change should also take in account delayed responses due to acclimation to abiotic stress or changing environmental conditions

Neural Network Analysis to Evaluate Ozone Damage to Vegetation Under Different Climatic Conditions

Tropospheric ozone (O-3) is probably the air pollutant most damaging to vegetation. Understanding how plants respond to O(3)pollution under different climate conditions is of central importance for predicting the interactions between climate change, ozone impact and vegetation. This work analyses the effect of O(3)fluxes on net ecosystem productivity (NEP), measured directly at the ecosystem level with the eddy covariance (EC) technique. The relationship was explored with artificial neural networks (ANNs), which were used to model NEP using environmental and phenological variables as inputs in addition to stomatal O(3)uptake in Spring and Summer, when O(3)pollution is expected to be highest. A sensitivity analysis allowed us to isolate the effect of O-3, visualize the shape of the O-3-NEP functional relationship and explore how climatic variables affect NEP response to O-3. This approach has been applied to eleven ecosystems covering a range of climatic areas. The analysis highlighted that O(3)effects over NEP are highly non-linear and site-specific. A significant but small NEP reduction was found during Spring in a Scottish shrubland (-0.67%), in two Italian forests (up to -1.37%) and during Summer in a Californian orange orchard (-1.25%). Although the overall seasonal effect of O(3)on NEP was not found to be negative for the other sites, with episodic O(3)detrimental effect still identified. These episodes were correlated with meteorological variables showing that O(3)damage depends on weather conditions. By identifying O(3)damage under field conditions and the environmental factors influencing to that damage, this work provides an insight into O(3)pollution, climate and weather conditions.Peer reviewe

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50x10e9/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (>2 points) versus 6.4% in the low-risk group (0–1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis

In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

Three-dimensional (3D)-printed medical-grade polycaprolactone (mPCL) composite scaffolds have been the first to enable the concept of scaffold-guided bone regeneration (SGBR) from bench to bedside. However, advances in 3D printing technologies now promise next-generation scaffolds such as those with Voronoi tessellation. We hypothesized that the combination of a Voronoi design, applied for the first time to 3D-printed mPCL and ceramic fillers (here hydroxyapatite, HA), would allow slow degradation and high osteogenicity needed to regenerate bone tissue and enhance regenerative properties when mixed with xenograft material. We tested this hypothesis in vitro and in vivo using 3D-printed composite mPCL-HA scaffolds (wt 96%:4%) with the Voronoi design using an ISO 13485 certified additive manufacturing platform. The resulting scaffold porosity was 73% and minimal in vitro degradation (mass loss <1%) was observed over the period of 6 months. After loading the scaffolds with different types of fresh sheep xenograft and ectopic implantation in rats for 8 weeks, highly vascularized tissue without extensive fibrous encapsulation was found in all mPCL-HA Voronoi scaffolds and endochondral bone formation was observed, with no adverse host-tissue reactions. This study supports the use of mPCL-HA Voronoi scaffolds for further testing in future large preclinical animal studies prior to clinical trials to ultimately successfully advance the SGBR concept

In BCR-ABL1 Positive B-Cell Acute Lymphoblastic Leukemia, Steroid Therapy Induces Hypofibrinogenemia

Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels of FBG during induction treatment and explore if the FBG fall correlated with therapies other than asparaginase and/or specific leukemia biological features. We retrospectively analyzed FBG levels in 115 patients with B-ALL. In 74 (64%) out of 115 patients FBG decline occurred during the steroid prephase. In univariate analysis, such a steroid-related HF was significantly associated with BCR-ABL1 rearrangement (p = 0.00158). None of those experiencing HF had significant modifications of liver function tests during induction treatment. Our retrospective study suggests that in B-ALL, steroid therapy can also induce HF and that such an event is preferentially observed in patients carrying BCR-ABL1 rearrangements. The pathogenesis of this phenomenon is still unclear. We attempt to explain it by applying the International Society of Thrombosis and Hemostasis-Disseminated Intravascular Coagulation score (ISTH-DIC score); nonetheless additional studies are needed to clarify further the mechanisms of HF in this subset of patients

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt